Peripheral Precocious Puberty Causes, Diagnosis and Management

Table of contents

1. I. Introduction

recocious puberty (pp) is a common problem seen in pediatric endocrinology practice. It is a complex and can be classified into, central precocious puberty, gonadotropin dependent or true PP which results from early maturation of hypothalammopituitary-gonadal (HPG) axis, and peripheral (pseudo) precocious puberty which is also known as gonadotropin independent puberty, is the result of autonomous peripheral secretion of excess sex hormones independent of the HPG axis. (1)(2)(3)(4)(5) The aim of this article was to discuss peripheral precious puberty and its diagnosis and management.

2. II. Materials and Methods

All patients diagnosed to have peripheral (pseudo) precocious puberty at the pediatric endocrine series of the King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia in the period January 1990 and December 2016, were retrospectively reviewed. Data included age, sex, clinical demographic data, hormonal and radiological investigations. The diagnosis was based on history, clinical examination, hormonal and radiological findings. Gonadotropin releasing hormone (GnRH) stimulation testing is considered as the gold standard for diagnosis (6)(7)(8). Radiological investigations (Pelvic Ultra Sonography), computed tomography (CT), and magnetic resonance imaging (MRI) were performed when indicated.

3. III. Results

During the period under review a total of 19 patients were diagnosed to have peripheral (pseudo) precocious puberty.

Fifteen girls and 4 boys. Their mean age was 3.5 (range; 0.5-7 years). Laboratory investigations revealed elevated Oestradiol level, mean: 110 ng/ ml (normal; up to 35) and testosterone mean: 2.1 nanomol/ L (normal; 0.1-0.4) with suppressed gonadotropin levels on GnRH stimulation test. The etiological diagnosis showed variety of causes (Table ).

Congenital adrenal hyperplasia and chronic hypothyroidism were the commonest found in eight and five patients respectively.

Tumors of the adrenal may cause virilization or feminization depending on weather androgens or estrogens are secreted, one estrogen secreting adenoma presented with feminization in a boy and two were due to adrenal carcinoma (figure).

Ovarian cyst and granulosa cell tumor were present in one paticient each. The classic triad of polyostotic fibrous dysplasia, Café/ au/ lait macules of the skin and precocious puberty indicates McCune-Albright syndrome, found in one girl.

4. IV. Discussion

Precocious puberty is defined as development of secondary sex characteristics before the age of eight years in girls and nine years in boys. Two types of precocious puberty are recognized; central (true) precocious puberty (CPP) and peripheral (pseudo) precocious puberty (PPP). CPP is caused by early activation of the hypothalamic-pituitary axes (HPA), with gonadotropin-releasing hormone (GnRh). Stimulated gonadotropin secretion causing gonads maturation. In PPP, serum sex steroids are elevated independent of gonadotropin secretion, and because gonadotropin levels are low the gonads do not undergo maturation. Precocious puberty may be isosexual (involving secondary sex characteristics that are gender matched) or heterosexual (involving sex characteristics of the opposite gender). CPP is always isosexual, whereas PPP may be isosexual or heterosexual.

In Saudi Arabia where the prevalence of consanguinity increased (9,10), congenital adrenal hyperplasia commonly causes virilization without testicular enlargement in boys, and girls will not have breast enlargement, unless secondary central precocious occurred. Approximately 40% of our patients in this series were due to congenital adrenal hyperplasia (21-? -hydroxylaze or 11? hydroxylase deficiency which is a common occurrence in Saudi Arabia and easily diagnosed. The treatment includes glucocorticoids, usually hydrocortisone 12-15 mg/m2/day (11,12). Severe chronic hypothyroidism rarely results in precocious puberty, and unlike other causes, is associated with skeletal and growth delay. The pathophysiology is uncertain, but it may be due to the intrinsic FSH activity if very high TSH levels. The signs of puberty is usually reversible with thyroxine therapy (13,14). Tumors of adrenal glands, ovary, or testes mat cause varilization or feminization depending on whether androgen or estrogen are secreted. These rare neoplasia require surgery or chemotherapy both. Also, Human Chorionic gonadotropin (hCG) secreting tumors can cause precocious puberty in boys by stimulating leydig cells to secrete testosterone. Unlike boys, girls with HCG secreting tumors generally do not develop precocious puberty. Both LH and FSH stimulation are necessary for ovarian activation. Raped varilization suggests the possibility of an endocrine secreting tumor. in adrenal tumors, both testosterone and Dehydroepiandrosterone are usually markedly elevated. A raised serum HCG suggests an hCG secreting tumors. ?? fetoprotein and carcinoembryonic antigen (CEA) are potentially useful markers of non germinomatous germ cell tumors. Ultrasonography helps in delineating the different causes (15)(16)(17) ovarian cysts occur in 2.5% if pre pubertal girls. Imaging studies (ultrasound help in differentiating benign/ malignant legions. Cysts having few internal echoes suggestive of hemorrhages with separation/ calcification is most benign and requires observation with follow up ultrasound in 1 to 2 months. Surgery may be required for large ovarian cyst (>20 ml) because the risk of adnexal torsion. Aromatase inhibiters are used in the management of persistent cyst. Recurrent or persistent ovarian cyst with a solid component in imaging suggest ovarian tumors. Juvenile granulosa cell tumors was the most common ovarian neoplasia to present with precocious puberty (17)(18)(19)(20)(21)(22). The McCune-Albright Syndrome causes precocious puberty, primarily in girls. The classic disorder comprises the triad of polyestotic fibrous dysplasia, café -au -Lait pigmentation, and gonadotropin independent precocious puberty. The disorder results from an activating somatic mutation in Gs, the protein that transduces the signal of many 7 -transmembrane domain receptors, including gonadotropin receptors. Testolactone and other anti-estrogen like Fudrozole and Tamoxifen are effective in treating girls with McCune-Albright syndrome. Unfortunately, escaping from the effects of treatment may occur after one to three years. After years of exposure to estrogen, many of these girls enter central precocious puberty and require treatment with LHRH analogue (23)(24)(25)(26).

5. V. Acknowledgement

Table 1: Etiology of peripheral, gonadotropin-independent, (pseudo) precocious puberty in 19 patients

6. Diagnosis

Male Female

Figure 1. Figure 1 :
1Figure 1: Computed tomography (CT) scan of abdomen reveals right adrenal mass which proved to be estrogen secreting abdomen.

Appendix A

Appendix A.1

The authors would like to thank Mr Mooath N Al-Jurayyan for his help in preparing this manuscript.

Appendix B

Appendix B.1 Conflict of interest

Funding None

Appendix C

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Date: 2017-01-15